1. Field of the Invention
The invention relates to a process for the preparation of alkyl and aryl esters of 3'-substituted and 2', 3'-disubstituted 2-anilino-3-pyridine carboxylic acids and more specifically relates to a process for the preparation of pivaloyloxymethyl and 3-phthalidyl esters of 2-[3'-(trifluormethyl) anilino]-3-pyridinecarboxylic and 2-(3'-chloro-2' methylanilino)-3-pyridinecarboxylic acids.
2. Brief Description of the Prior Art
The prior art includes literature teaching the synthesis and use of alkyl and aryl esters of 3'-substituted and 2', 3'-disubstituted 2-anilino-3-pyridine carboxylic acids. For example, the preparation of 2-(3' chloro-2'-methyl-anilino)-3-pyridinecarboxylic acid, an analgesic agent, was disclosed in British Pat. No. 1.147.702. Also, the synthesis of 2-[3'-trifluoromethyl) anilino]-3-pyridinecarboxylic acid, an antiinflammatory agent, was described in Dutch Pat. No. 6.414.717 and Argentine Pat. No. 183.423.
These 3' and 3', 2'-substituted 2-anilino-3-pyridinecarboxylic acids present in addition to their antiinflammatory and analgesic properties, an ulcerogenic effect on the gastric epithelium. To diminish such side-effects several related derivatives were synthesized. For example, aminoalkyl esters of 2-anilino-nicotinic acids are described in French Pat. No. 2.187.317. Glyceryl esters of the same acids are disclosed in Swiss Pat. No. 534.130 and South African Pat. No. 68 2185. Also, different salts of substituted 2-anilino-3-pyridine-carboxylic acids were described; e.g. ethanolamine, lysine, aluminium and bismuth salts are disclosed in Argentine Pat. No. 182.409, Japanese Pat. No. 74 075713 and British Pat. No. 1.162.287.
The present invention concerns a new process for preparing esters of the above-described acids which lack the characteristic side-effects presented by analgesic and antiinflammatory acids from which these esters are derived (Scherrer, R. A., Whitehouse, M. W., Antiinflammatory Agents, Chemistry and Pharmacology, 13-1, Academic Press, New York, 1974).
Compounds produced by the method of the invention are antiinflammatory agents which exhibit lessened ulcerogenic effects.